PEPTIDE-INDUCED POSITIVE SELECTION OF TCR TRANSGENIC THYMOCYTES IN A CORECEPTOR-INDEPENDENT MANNER

T cell receptor (TCR) transgenic thymocytes specific for the LCMV gp p eptide are normally positively selected to the CD8 lineage. Transgenic thymocyte development was substantially reduced in the absence of the se CD8 coreceptors. However, efficient positive selection was restored when TCR transgenic CD8(-/-) fetal thymic lobes were cultured with a peptide variant of the wild-type ligand. These mature thymocytes were functional, as shown by their ability to respond against strong peptid e agonists. Additional experiments demonstrated that transgenic positi ve selection was peptide-specific. These results prove that CD8 does n ot possess essential signaling properties that are necessary for T cel l development. In addition, the unilateral commitment of transgenic th ymocytes to mature CD4(-)TCR(hi) T cells expressing intracellular perf orin suggests that there must be some instructive component to CD4 dow n-regulation and lineage commitment during thymocyte selection.